CRYSTAL MODIFICATION OF ATOVAQUONE IN PRESENCE OF POLYETHYLENE GLYCOL (PEG) 4000

Atovaquone is a hydroxynaphthoquinone that has antimicrobial activity and is being used in antimalarial protocols. Its inhibitory effect being comparable to ubiquinone, in sensitive parasites atovaquone can act by selectively affecting mitochondrial electron transport and parallel processes such as ATP and pyrimidine biosynthesis. It exhibits low bioavailability related to its poor water solubility. The present research investigates crystal modification of atovaquone to improve the solubility, dissolution rate as well as some physicochemical properties. The crystals were modified in presence of PEG-4000. The modified crystals were characterized by Scanning electron microscopy, FT-IR spectroscopy, differential scanning calorimetry and X-ray diffraction. The solubility and dissolution rate of modified crystals were compared with untreated atovaquone. The SEM results showed different morphology of modified crystals compare to untreated atovaquone. FT-IR spectra of untreated atovaquone when compared with modified crystals showed no significant change in their characteristic peaks. Also DSC spectra showed change in the melting endotherm of modified crystals and the XRD spectra revealed change in diffraction pattern. The FT-IR, DSC and XRD indicate crystal modification in the presence of PEG 4000. The modified crystals obtained in the presence of PEG 4000 showed improved solubility and dissolution rate compare to untreated atovaquone.